Symptomatic Intracranial Arterial Stenosis Lessons from SAMMPRIS

Symptomatic Intracranial
Arterial Stenosis:
Lessons from SAMMPRIS
Andrew Russman, D.O.
Director, Stroke Program, West Bloomfield Hospital
Senior Staff Neurologist, euoogs, Harris sStroke eCenter
e
Assistant Professor, Wayne State University

Disclosures
• I am NOT paid to do endovascular
procedures.
• Research funding: Harris Stroke Fund
and NIH/NINDS Henry Ford NETT
Grant.

Learning Objectives
Upon completion of fthis session, participants
i t
should be able to:
• Describe the high-risk symptomatic
intracranial disease patient
• Interpret the results of the SAMMPRIS
Trial
• Identify future directions in symptomatic
intracranial disease management

Burden of Atherosclerotic
Intracranial Stenosis
• Important tcause of stroke in certain ethnic or
racial groups (Black, Hispanic, or Asian descent)
• 90,000000 patients with TIA or Stroke / year in USA
• Approximately 50,000 strokes per year at a cost of
$750 million in 1 year and $4.5 billion over the
lifetime of these patients
• Based on ethnic and racial make-up of world
population, may be most important cause of stroke

90% stenosis

First Paper to Suggest Role for
Anticoagulation
MILLIKAN CH, SIEKERT RG, SHICK RM.
Studies in cerebrovascular disease. III. The
use of anticoagulant tdrugs in the treatment
t t
of insufficiency or thrombosis within the
basilar arterial system. Proc Staff Meet
Mayo Clin. 1955 Mar 23;30(6):116-26.

WASID Trial
Pi Primary Endpoint: Stroke and dV Vascular Death
Probab bility of Stroke / Vascular Death
0.4
0.3
0.2
0.1
0
p = 0.82
0 1 2 3 4 5
Aspirin
Warfarin
Years after Enrollment

WASID Trial
Secondary Endpoint: Major Hemorrhages and Death
Aspirin
Events /
100 pt.yrs
Warfarin p-
Events /
value
100 pt.yrs
Major Hem. 1.8 4.4 0.01
Death 2.4 24 52 5.2 002
0.02

WASID: Impact on Clinical Practice
Preferred Rx MCA or Siphon
Warfarin
Antiplatelet**
U.S. Stroke
Neurologists
(n=170)
Pre / Post
43% / 7%
44% / 86%
Combination 12% / 3%
Preferred Rx Vert. or Basilar
Warfarin
Antiplatelet**
Pre / Post
50% / 15%
37% / 74%
Combination 12% / 6%
** aspirin used most commonly

WASID: Risk Factor Control
Chaturvedi et al (WASID), Neurology
2007

WASID: Ischemic Stroke Risk Factors
Risk Factor
(RF)
Event Rate
Event Rate
+ RF -RF
Hazard
Rate,
P-value
SBP > 140 23% 15% 1.6 (1.1-2.4)
P=0.012
LDL > 100 19% 12% 17(104
1.7 (1.04-
2.9)
P=0.033
LDL > 70 17% 7% 2.3 (0.6-9.4),
p= 0.23

WASID: Risk of Stroke in Symptomatic Vessel
WASID S t ti V l
WASID Symptomatic Vessel
1 year rate
>70% stenosis = 18%
Vs.
< 70% stenosis = 7-8%

WASID: Combining 70-99% Stenosis
and Time from Qualifying Event to Enrollment
1 year
30 days
22.9 %
(95% CI 15.4 – 30.4%)
9%
> 30 days (95% CI 2.1 – 16.0%)

Is There a Role for Endovascular Rx?

Patient
Characteristics
Wingspan Stent Registry
4-Center Registry
(n = 158 )
50-99% stenosis (2/3
> 70%) and TIA /
stroke on Rx
NIH Wingspan
registry
(n = 129 )
70-99% stenosis and
TIA / stroke on Rx
Technical Success 98.8% 96.7% (91.8 – 99.1%
Stroke or death rates:
24 hours
30 days
+ ipsilat stroke at 6
months
-
61%
6.1%
-
6.2% (3.2 – 12%)
96%(56 9.6% (5.6 – 16.3%)
14% (8.7 – 22.1%)
> 50% restenosis 30% 25%

Study Design
Angioplasty and Stenting (Wingspan System) +
Aggressive Medical Management
Vs.
Aggressive Medical Management alone
• Target Sample Size = 764 patients
• Main Inclusion Criteria:
−
−
70 - 99% stenosis
Recent (within 30 days) non-disabling stroke or TIA

Aggressive Medical Management
• Aspirin 325 mg / day for entire follow-up
• Clopidogrel 75mg per day for 90 days
• Aggressive, protocol driven risk factor management
primarily targeting systolic blood pressure < 140 mm Hg
(130 mm Hg diabetics) and low density cholesterol < 70
mg / dl
• Intervent USA – a lifestyle modification program

• DSMB / NINDS stopped enrollment at
451 patients t on April 5, 2011 primarily
il
because of safety (high stroke and death
rate after stenting)

SAMMPRIS: Baseline Patient Characteristics
Characteristic
Age (Yrs)
Gender (Male)
Medical Group PTAS Group
(N=227)
(N=224)
59.55 61.0
145 (64) 127 (57)
Race
Black
50 (22)
55 (25)
White
161 (71) 160 (71)
Other
16 (7)
9 (4)
Chimowitz MI, et al. N Engl J Med 2011; 365:993-1003.

SAMMPRIS: Baseline Patient Characteristics
Characteristic
Medical Group
(N=227)
PTAS Group
(N=224)
Hypertension (Yes) 203 (89) 201 (90)
Diabetes (Yes) 103 (45) 106 (47)
Lipid Disorder (Yes) 203 (89) 194 (87)
Smoking
Never
Previously
Currently
78 (34) 90/223 (40)
80 (35)
79/223 (35)
69 (30)
54/223 (24)
History of Coronary Artery
Disease (Yes) 59 (26) 47 (21)
History of Stroke (Not
Qualifying Event) (Yes) 58 (26) 60 (27)
Chimowitz MI, et al. N Engl J Med 2011; 365:993-1003.

Achievement of Target
Levels
30
days
* As of 12/29/11. Data collection ongoing.

Achievement of Target
Levels
% of patien nts in targe et
100
90
80
70
60
50
40
30
20
10
% of patients meeting SECONDARY risk factor targets in
SAMMPRIS*
smoking
physical activity
HgA1c (diabetics only)
weight
0
0 2 4 6 8 10 12 14 16 18 20
30
days
months
* As of 12/29/11. Data collection ongoing.

SAMMPRIS Results: 30-Day Outcome
• 14.7% (n = 33) of patients treated with PTAS
experienced a stroke or died
versus
• 5.8% (n = 13) of patients treated with AMM alone
p = 0.002

Symptomatic Brain Hemorrhages Within 30 Days
10 * of 33 (30.3%) strokes in the PTAS group
0 of f12 (0%) strokes in the AMM group
Significant difference, p = 0.04
* Of 10 hemorrhages, 4 were fatal and 4 were disabling

Types of Ischemic Strokes Within 30 days
of fPTAS
• Ischemic:
• 12 perforator level
• 3 embolic
• 2 mixed perforator and embolic
• 2 delayed in-stent thrombotic occlusions
• 3 after angiography only (1 procedure related, 2
from occlusion days later)

Perforator: Treated 4 days after TIA
with cortical blindness, dizziness,
nausea and vomiting, left side
paresthesias (MR negative).
No problems evident during the
procedure, excellent result.
Dysarthria and left hemiparesis
several hours after the procedure and
vertical diplopia the next day.
mRS = 2 at 30 days (0 at entry)

SAMMPRIS Results >30 days
Beyond 30 days, the rates of stroke
in the territory of the stenotic artery
are similar il in the two groups
(13 in each group)
*fewer than half the patients have been followed for one year

1-year rate of the primary endpoint
• 20.0% in PTAS group
• 12.2% in AMM group

SAMMPRIS Conclusions
Based on current data:
Aggressive medical therapy (AAM)
is SUPERIOR
to PTAS using the Wingspan system
in high-risk patients with intracranial stenosis
(Follow-up continuing until March 2013)

Lessons from SAMMPRIS
• “SAMMPRIS-eligible ibl patients t should be
treated with a SAMMPRIS-like medical
regimen.”
– Colin Derdeyn, M.D., Neuro-interventional-PI
– SAMMPRIS Trial

90% stenosis

Unfinished Business
• Are There Subgroups of Patients Treated with
Aggressive Medical Management Who Are Still at
High-Risk?
– Possible groups include hemodynamic impairment
(Liebeskind D, ISC abstract)
– No clear subgroup has emerged from review of
SAMMPRIS data yet
• Other Options
– Medical - Direct Thrombin or Xa inhibitors?
– Endovascular – Angioplasty Alone, New stents?
• WASID High-Risk population had a 1-year stroke rate of 12%
WASID High-Risk population had a 1-year stroke rate of 12%
in SAMMPRIS (unlikely to show benefit in this group)

Aggressive Medical Therapy